Biallelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome
Am J Hum Genet. 2023 Nov 7:S0002-9297(23)00366-X. doi: 10.1016/j.ajhg.2023.10.013. Online ahead of print. ABSTRACT Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance […]
A genetics-guided approach to the clinical management of schizophrenia
Schizophr Res. 2023 Oct 7:S0920-9964(23)00353-5. doi: 10.1016/j.schres.2023.09.042. Online ahead of print. ABSTRACT Schizophrenia is a highly heritable, severe mental illness characterized by hallucinations, delusions, social withdrawal, and cognitive dysfunction present in ∼1% of populations across cultures. There have been recent major advancements in our understanding of the genetic architecture of schizophrenia. Both rare, highly penetrant […]
Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease
medRxiv. 2023 Oct 5:2023.10.05.23296595. doi: 10.1101/2023.10.05.23296595. Preprint. ABSTRACT Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and with new innovative methods can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort […]
The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief
National Academies of Sciences, Engineering, and Medicine. 2023. The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/2724 Pilot programs are employing whole genome sequencing and whole exome sequencing during the newborn phase both within the United States and internationally. While sequencing offers the […]
An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges
J Clin Transl Sci. 2023 Sep 14;7(1):e214. doi: 10.1017/cts.2023.619. eCollection 2023. ABSTRACT Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As […]
Unique Challenges of NIPT for Sex Chromosome Aneuploidy
Clin Obstet Gynecol. 2023 Sep 1;66(3):568-578. doi: 10.1097/GRF.0000000000000804. Epub 2023 Jul 24. ABSTRACT Noninvasive prenatal testing (NIPT) for the sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, and 47,XYY) differs significantly from that for the autosomal aneuploidies (trisomy 13, 18, and 21). As a group, sex chromosome aneuploidies occur more commonly (1/400) than any one isolated autosomal […]
Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome
Am J Med Genet A. 2023 Aug 19. doi: 10.1002/ajmg.a.63363. Online ahead of print. ABSTRACT Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of […]
Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies
Brain Commun. 2023 Aug 17;5(5):fcad222. doi: 10.1093/braincomms/fcad222. eCollection 2023. ABSTRACT LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific […]
Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis
medRxiv. 2023 Aug 13:2023.08.08.23293829. doi: 10.1101/2023.08.08.23293829. Preprint. ABSTRACT BACKGROUND: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages […]
Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders
Brain. 2023 Jul 30:awad257. doi: 10.1093/brain/awad257. Online ahead of print. ABSTRACT MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia. We further delineate the clinical phenotype of […]